Rational Engineering of Secondary Metabolic Pathways in a Heterologous Host to Enable the Biosynthesis of Hibarimicin Derivatives with Enhanced Anti-Melanomic Activity

A 61-kb biosynthetic gene cluster(BGC),which is accountable for the biosynthesis of hibarimicin(HBM)B from Microbispora rosea subsp.hibaria TP-A0121,was heterologously expressed in Streptomyces coelicolor M1154,which generated a trace of the target products but accumulated a large amount of shunt products.Based on rational analysis of the relevant secondary metabolism,directed engineering of the biosynthetic pathways resulted in the high production of HBM B,as well as new HBM derivates with improved antitumor activity.These results not only establish a biosynthetic system to effectively synthesize HBMs-a class of the largest and most complex Type-Ⅱpolyketides,with a unique pseudo-dimeric structure-but also set the stage for further engineering and deep investigation of this complex biosynthetic pathway toward potent anticancer drugs.

Approximate solution of Volterra-Fredholm integral equations using generalized barycentric rational interpolant

It is well-known that interpolation by rational functions results in a more accurate approximation than the polynomials interpolation.However,classical rational interpolation has some deficiencies such as uncontrollable poles and low convergence order.In contrast with the classical rational interpolants,the generalized barycentric rational interpolants which depend linearly on the interpolated values,yield infinite smooth approximation with no poles in real numbers.In this paper,a numerical collocation approach,based on the generalized barycentric rational interpolation and Gaussian quadrature formula,was introduced to approximate the solution of Volterra-Fredholm integral equations.Three types of points in the solution domain are used as interpolation nodes.The obtained numerical results confirm that the barycentric rational interpolants are efficient tools for solving Volterra-Fredholm integral equations.Moreover,integral equations with Runge’s function as an exact solution,no oscillation occurrs in the obtained approximate solutions so that the Runge’s phenomenon is avoided.

Experimental study of core MHD behavior and a novel algorithm for rational surface detection based on profile reflectometry in EAST

Microwave reflectometry is a powerful diagnostic that can measure the density profile and localized turbulence with high spatial and temporal resolution and will be used in ITER,so understanding the influence of plasma perturbations on the reflect signal is important.The characteristics of the reflect signal from profile reflectometry,the time-of-flight(TOF)signal associated with the MHD instabilities,are investigated in EAST.Using a 1D full-wave simulation code by the Finite-DifferenceTime-Domain(FDTD)method,it is well validated that the local density flattening could induce the discontinuity of the simulated TOF signal and an obvious change of reflect amplitude.Experimental TOF signals under different types of MHD instabilities(sawtooth,sawtooth precursors and tearing mode)are studied in detail and show agreement with the simulation.Two new improved algorithms for detecting and localizing the radial positions of the low-order rational surface,the cross-correlation and gradient threshold(CGT)method and the 2D convolutional neural network approach(CNN)are presented for the first time.It is concluded that TOF signal analysis from profile reflectometry can provide a straightforward and localized measurement of the plasma perturbation from the edge to the core simultaneously and may be a complement or correction to the q-profile control,which will be beneficial for the advanced tokamak operation.

Blockchain-Based Key Management Scheme Using Rational Secret Sharing

Traditional blockchain key management schemes store private keys in the same location,which can easily lead to security issues such as a single point of failure.Therefore,decentralized threshold key management schemes have become a research focus for blockchain private key protection.The security of private keys for blockchain user wallet is highly related to user identity authentication and digital asset security.The threshold blockchain private key management schemes based on verifiable secret sharing have made some progress,but these schemes do not consider participants’self-interested behavior,and require trusted nodes to keep private key fragments,resulting in a narrow application scope and low deployment efficiency,which cannot meet the needs of personal wallet private key escrow and recovery in public blockchains.We design a private key management scheme based on rational secret sharing that considers the self-interest of participants in secret sharing protocols,and constrains the behavior of rational participants through reasonable mechanism design,making it more suitable in distributed scenarios such as the public blockchain.The proposed scheme achieves the escrow and recovery of personal wallet private keys without the participation of trusted nodes,and simulate its implementation on smart contracts.Compared to other existing threshold wallet solutions and keymanagement schemes based on password-protected secret sharing(PPSS),the proposed scheme has a wide range of applications,verifiable private key recovery,low communication overhead,higher computational efficiency when users perform one-time multi-key escrow,no need for trusted nodes,and personal rational constraints and anti-collusion attack capabilities.

Smoking of Carica papaya in Nigeria:The rationale,the public health effects and policies for intervention

Psychoactive substance use is characterized by the habitual use of substances that have significant effects in altering the activities of neurotransmitters in certain regions of the brain.Consequently,these alterations manifest as cognitive,emotional,perceptual and behavioural changes in affected individuals[1].

Practice of Perioperative Rational Use of Antibacterial Drugs Based on Drug Pathway

[Objectives]To establish a new management model for rational use of perioperative antibacterial drugs in surgical departments.[Methods]Based on evidence-based medicine,the department s drug pathway was formulated,and the new mode of rational drug use control was established by using fine pharmaceutical technology intervention,and the intervention effect was evaluated by the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs.[Results]After adopting drug pathway in departments,the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs decreased significantly,and the effect of rational drug use control was remarkable.[Conclusions]The drug pathway provides a new management and control mode for the rational use of perioperative antibacterial drugs in surgical departments of hospitals.Thus,it is worthy of popularization and application.

Exact controllability of rational expectations model with multiplicative noise and input delay

This paper considers the rational expectations model with multiplicative noise and input delay,where the system dynamics rely on the conditional expectations of future states.The main contribution is to obtain a sufficient condition for the exact controllability of the rational expectations model.In particular,we derive a sufficient Gramian matrix condition and a rank condition for the delay-free case.The key is the solvability of the backward stochastic difference equations with input delay which is derived from the forward and backward stochastic system.

Rationale and Pathway for New Industrialization in the Context of Chinese Modernization

The concepts of modernization and industrialization have different connotations that are specific to their historical backgrounds,and their theoretical innovation and development may benefit from China’s experiences.Industrialization is the cornerstone of modernization,and holds the key to its success.China’s experiences in blazing a new trail of industrialization are challenging the traditional Western theory of industrialization and deepening the connotations of Chinese modernization.New industrialization is a key entry point for steering China’s modernization drive and theoretical innovations.This paper offers an overview of the theory of Chinese modernization and its evolving trend along China’s socialist industrialization path,as well as the rationale and pathway for new industrialization in the context of Chinese modernization.As our findings suggest,the new industrialization concept has taken hold in every key aspect of Chinese modernization.When combined with the theory of Chinese modernization,the theoretical implications of new industrialization play a crucial role in propelling Chinese modernization forward along a new journey in the new era.

The Global Security Initiative: Its Relevance, Rationale and Delivery

Today,our world is undergoing profound changes unseen in a century.Global security landscape is becoming ever more unstable and uncertain.In the face of growing deficits in security,Chinese President Xi Jinping put forward the Global Security Initiative(GSI),offering a clear answer to the question of the times:what kind of security concept does the world need,and how can we achieve common security?It is of great significance to fully grasp the relevance of and the rationale for the GSI,and push for its strategic delivery,so as to contribute to the long-term peace and stability of the world.

The Frontiers and Future Landscape of Research and Education on Value Rationality in Contemporary China

The importance of conducting in-depth research and education on value rationality in the new era is increasingly recognized.Therefore,it is essential to systematically grasp the themes,frontiers,and trends of research in this field,organizing the knowledge system to provide references for future studies.This necessitates clarifying the research achievements of scholars from different disciplines and institutions.Using the CiteSpace visualization analysis method,we can analyze,summarize,and synthesize research networks,hotspots,and knowledge structures,thereby forming a direction for advancing research.Through literature review methods and knowledge graph software analysis,it is believed that value rationality and instrumental rationality represent the rational attitudes individuals adopt when contemplating issues and putting them into practice.They are merely methods and should not be subjected to excessive value judgments.The relationship between value rationality and instrumental rationality is a focal point of societal concern,involving complex interdisciplinary issues with significant theoretical value and practical implications.In the future,the academic community needs to strengthen research collaboration,enhance the expansion of value rationality in various social practice fields,and conduct empirical studies to build consensus for the construction of Chinese society.

Evaluation of the Effectiveness of Community Pharmacy Services on Rational Medication Use in Elderly Patients with Hypertension and Diabetes

Objective:To explore the effect of community pharmacy services on rational medication use in elderly patients with hypertension and diabetes.Methods:Between November 2022 and December 2023,80 elderly patients with hypertension and diabetes were selected and randomly divided into a control group(routine medication guidance)and an observation group(community pharmacy services),with 40 subjects each.The medication effect scores,blood pressure,blood sugar levels,and quality of life scores before and after intervention were compared between the two groups.Results:Comparison of pharmaceutical knowledge,medication compliance,and safe medication behavior scores showed that the observation group had higher scores as compared to the control group(P<0.05);blood pressure(systolic blood pressure,diastolic blood pressure,heart rate)and blood sugar(fasting blood glucose,2 h postprandial blood glucose,glycated hemoglobin)index levels were compared,and the observation group’s index levels were lower than those of the control group(P<0.05);the scores of physical health,mental health,social relationships,and environment in the observation group were higher than those in the control group(P<0.05).Conclusion:Community pharmacy services improved the rational medication effect of elderly patients with hypertension and diabetes,and improved their blood pressure,blood sugar control levels,and quality of life.

Embodiment of Rationality:Philosophical Interpretation of Embodied Cognition

Under the influence of European rationalism,which holds that human rationality is higher than,or at least independent of human sensory cognition,the first generation of cognitive science advocates for disembodied cognition,manifesting the concept of dualism of mind and body.With the development of cognitive science in the 1980s,the second generation of cognitive science redefines the relationship between mind and body,thought and behavior,and reason and feeling and puts forward the concept of embodied cognition,representing monism of mind and body.It is claimed that the formation of concepts,categorical cognition and the evolution of rational thinking are characterized by embodiment,which is the necessary condition and basis for the formation of human rationality.The current study traces the shift of cognitive science from dualism to monism of mind and body and explores the relationship between rationality and sensibility from the perspective of philosophical basis and interpretations,with an aim to achieve a better understanding and thorough interpretation of human rationality.In this heated discussion about embodied cognition,there are still some fundamental questions that need to be further clarified,such as the essence and mechanism of human cognition,the ways that human body participates in cognitive activities,especially imagination and reasoning.The research paradigm of embodied cognition and its relevant theory have not been established and developed yet,and empirical research from interdisciplinary perspectives is far from enough to provide hard evidence for embodied cognition.

Rational Design of Grain Size to Improve Rice Yield and Quality

Grain size, determined by grain length, grain width and grain thickness, is associated with grain yield and quality. Many genes controlling grain size were cloned and their related regulatory mechanisms were clearly clarified. However, whether these genes can be directly introduced into japonica rice for grain size improvement is unknown.

Rational solutions of Painlevé-Ⅱequation as Gram determinant

Under the Flaschka-Newell Lax pair,the Darboux transformation for the Painlevé-Ⅱequation is constructed by the limiting technique.With the aid of the Darboux transformation,the rational solutions are represented by the Gram determinant,and then we give the large y asymptotics of the determinant and the rational solutions.Finally,the solution of the corresponding Riemann-Hilbert problem is obtained from the Darboux matrices.

Present situation of rational drug use in plateau area

Plateau is characterized by low oxygen,low pressure,strong radiation,cold and dryness,among which low oxygen is the main factor that affects the normal life activities of human body.Altitude hypoxia leads to significant changes in the metabolic characteristics of drugs in vivo,which in turn affects the efficacy and adverse actions of drugs.This paper summarizes the present situation of rational drug use in plateau area and pinpoints the existing problems.Meanwhile,we posit the strategies and measures for realizing rational and precise pharmacotherapy of plateau residents.First,we need to acquire a panoramic view of differential and relative pharmacokinetics and pharmacodynamics in between plateau area and plain area by carrying out comparative studies on drug metabolisms and on comprehensive drug efficacies and mechanisms.Second,we must apply the findings from basic research to clinical practice and formulate guidelines and recommendations of drug use for plateau habitants.Finally,we should eventually achieve precise and individualized drug use for plateau habitants based on their characteristic etiology and pathogenesis.

Investment Promotion for Development Zones in China:Underlying Rationale and Policy Options

Development zones(DZs)have emerged as a significant policy initiative for promoting regional coordination and facilitating resources allocation.They serve as an organizational framework for fostering industrial agglomeration and driving high-quality development.DZs attract and accommodate resource factors,firms,and projects,thereby functioning as a central catalyst for economic growth.This study utilizes data collected at the“DZ,City and Countrycountry”levels through manual compilation,textual analysis,and innovation measurement.It aims to empirically examine the theoretical rationale and practical preferences for promoting business and investment in China’s DZs.This study considers several factors such as industry attribute,firm attribute,agglomeration theory,and industrial chain layout.Based on our research findings,DZs exhibit distinct preferences.First,industry attribute:DZs align with both national and regional strategic planning and adhere to the industrial endowments of the respective areas.Second,firm attribute:DZs prioritize attracting firms that are productive and innovative,and have an international presence,rather than those that primarily contribute to taxes and job creation.Third,DZs are guided by the agglomeration theory,which suggests that they prefer firms that generate strong agglomeration externalities.Lastly,DZs also consider the industrial chain layout,aiming to attract firms that not only align with their existing industrial strengths but also extend to the upstream and downstream supply chain links.These conclusions are substantiated by the performance of robustness test.The success of DZs in China can be attributed to the five key principles:Adherence to national and regional strategic planning,prioritizing the actual industrial foundation,incorporating the theory of agglomeration externalities,strengthening corporate competitiveness,and expanding industrial chains.

Analysis on Value Rationality of Traditional Farm Tools in the Taomin Area

This paper introduces the types of traditional farm tools,and analyzes the value rationality of these traditional farm tools:on the one hand,these farm tools have witnessed the farming culture,and they are also a manifestation of local culture in the Taomin area,representing the cultural characteristics and civilization progress of this area.

Estimating Sums of Convergent Series via Rational Polynomials

Sums of convergent series for any desired number of terms, which may be infinite, are estimated very accurately by establishing definite rational polynomials. For infinite number of terms the sum infinite is obtained by taking the asymptotic limit of the rational polynomial. A rational function with second-degree polynomials both in the numerator and denominator is found to produce excellent results. Sums of series with different characteristics such as alternating signs are considered for testing the performance of the proposed approach.

The reduction of tea quality caused by irrational phosphate application is associated with anthocyanin metabolism

Phosphorus(P)is the second most limiting nutrient for plant growth.Previous studies suggested that P substantially affects the yield and quality of tea by affecting root growth,the decomposition and metabolism of minerals and metabolites in plants.Thus,the environmental pollution and degradation of crop quality caused by irrational fertilization is of increasing interest for researchers worldwide.To understand the effects of P fertilization on tea quality and metabolism of key quality components,three P fertilization levels(excessive,appropriate,and deficient application)were applied to tea plants using pot experiments.Content of P,potassium,polyphenols,amino acids and anthocyanins in the leaves or soil were quantified.The sensory quality of tea infusion was reduced under irrational(excessive or deficient)P fertilization.Under P deficiency,the total content of polyphenols and anthocyanins in the leaves were strongly increased compared with those of the control.A high soil P content(excessive)inhibited polyphenol accumulation,but induced the accumulation of certain anthocyanins,such as peonidin-3-Osambubioside-5-O-glucoside and peonidin-3-O-5-O-(6-O-p-coumaryl)-diglucoside.These results suggest that the reduction of tea quality caused by irrational P application is associated with anthocyanin metabolism,which provides a scientific basis for improving P fertilization strategies in tea plantations.

The Level of Knowledge, Behaviors, and Attitudes on Rational Use of Drugs of Patients Who Applied to the Family Health Center in Istanbul, Türkiye: A Cross-Sectional Study

Background: This study, it was aimed to determine the level of knowledge, attitudes, and behaviors of patients who applied to a family health center about the rational use of drugs. Irrational use of drugs is a major problem worldwide. WHO reports that half of the patients do not use their drugs correctly. Methods: This cross-sectional study was conducted between 1 October 2017 and 30 November 2018 at Istanbul Fatih Family Health Center No 7. The sample size was determined as 301 people selected by systematic sampling method from patients aged 18 and older. Results: The mean age of the participants was 53.8% ± 16.8%, 59.8% were female, 62.5% were married, and 52.5% were primary school graduates. 63.9% of the participants knew the names of the drugs they used, and 79.9% of them knew the indication for use. 89% of individuals check the expiry date of the drugs before using them, and 83.1% read the drug prospectus. 84% of the participants support the prohibition of using over-the-counter drugs. Conclusion: The level of knowledge of the participants about the rational use of drugs is above the societal average. However, some issues need more awareness. The high level of rational use of drugs awareness of physicians and pharmacists will also strengthen the rational use of drugs and indirectly increase the awareness of the public.